J Cancer 2021; 12(3):717-725. doi:10.7150/jca.50483

Research Paper

Nogo-B receptor is required for stabilizing TGF-β type I receptor and promotes the TGF-β1-induced epithelial-to-mesenchymal transition of non-small cell lung cancer

Donghua Wu1#, Baofeng Zhao2#, Yang Song1, Xinming Chi1, Hailu Fu1, Tiantong Guan1, Liyuan Zhang1, Xueguang Yang1, Ke Hu1, Rong Huang1, Xiaomeng Jin1, Qing Robert Miao3,4,5,6✉, Shujuan Shao1✉

1. Key Laboratory of Proteomics of Liaoning Province, Dalian Medical University, Dalian 116044, China.
2. CAS Key Laboratory of Separation Sciences for Analytical Chemistry, National Chromatographic R&A Center, Dalian Institute of Chemical Physics, Chinese. Academy of Sciences, Dalian 116023, China.
3. Division of Pediatric Surgery, Department of Surgery, Children's Research Institute, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
4. Divisions of Pediatric Pathology, Department of Pathology, Children's Research Institute, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
5. Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
6. Foundations of Medicine, New York University Long Island School of Medicine, Mineola, NY 11501, USA.
#These authors have contributed equally to this work.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Citation:
Wu D, Zhao B, Song Y, Chi X, Fu H, Guan T, Zhang L, Yang X, Hu K, Huang R, Jin X, Miao QR, Shao S. Nogo-B receptor is required for stabilizing TGF-β type I receptor and promotes the TGF-β1-induced epithelial-to-mesenchymal transition of non-small cell lung cancer. J Cancer 2021; 12(3):717-725. doi:10.7150/jca.50483. Available from https://www.jcancer.org/v12p0717.htm

File import instruction

Abstract

Background and Objective: Metastasis is the leading cause of death in patients with advanced non-small cell lung cancer (NSCLC), and epithelial-mesenchymal transition (EMT) is a crucial event in the metastasis of NSCLC. Our previous works demonstrated that NgBR promoted EMT in NSCLC. However, the molecular mechanism was unclear.

Methods: TGF-β1 was used to induce EMT process of NSCLC cells. The biological functions of NgBR in promoting TGF-β1-induced NSCLC metastasis were studied by gain- and loss-of-function assays both in vitro and in vivo. The underlying mechanisms were studied using molecular biology assays.

Results: We found that knockdown of NgBR inhibited TGF-β1-induced cell migration and invasion in NSCLC cells. In contrast, NgBR overexpression promoted TGF-β1-induced EMT of A549 cells. Mechanically, we found that knockdown of NgBR facilitated ubiquitination and degradation of TβRI, leading to downregulation of TβRI expression in NSCLC cells. Moreover, we confirmed a positive correlation between NgBR and TβRI in NSCLC tissues.

Conclusions: Our findings provide a novel role of NgBR in modulating TGF-β1-induced EMT and propose NgBR as a new therapeutic target for treating NSCLC patients.

Keywords: Non-small cell lung cancer, Nogo-B receptor, Metastasis, Epithelial-mesenchymal transition, Transforming growth factor-β signal pathway